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Purpose: To evaluate a new cultivated coral graft (CCG) in an in vivo experimental guided bone regeneration (GBR) procedure. Materials and Methods: The calvarias of eight rabbits were surgically exposed, and circular defects 8 mm in diameter were prepared. One defect was filled with CCG particles (experimental group); the contralateral defect (control group) was spontaneously filled by blood clot. All defects were covered with a collagen membrane. Subjects were euthanized after 8 weeks. Results: Histologic observations of the defects showed similar bone growth patterns in both experimental and control osteotomies. In the experimental defects, no traces of coral particles were observed. Histometric analysis showed denser bone in the pristine zone (65%-66%) than in the peripheral zone for both the control (50%) and experimental defects (31%) (P = not significant). The new bone percentage was reduced from the peripheral zone toward the middle and the center of the defect (31%, 32%, and 27%, respectively) as the distance from the peripheral pristine bone borders increased. Conclusions: The existing data supports the complete degradation of CCG as a space-maintaining scaffold for GBR procedures. [ABSTRACT FROM AUTHOR]

Purpose: To assess the healing process of the extraction socket and the dimensional changes that occur after alveolar ridge preservation utilizing a polylactide-co-glycolide scaffold (PLGA). Materials and Methods: The present study involved the extraction of 28 teeth from 14 patients. The total number of sockets was 28, which were divided into two groups consisting of 14 test sockets and 14 control sockets. The study group (SG) was subjected to socket preservation with a PLGA scaffold while the control group (CG) was left for spontaneous healing. The dimensions were measured before and after operation at 1, 3, and 5 mm below the alveolar crest horizontally and the height of buccolingual bone vertically. Results: According to the histologic analyses, the PLGA scaffold was resorbed within 4 months. CBCT imaging revealed a decrease in the horizontal crest dimension at three distinct coronoapical levels in SG, measuring 2.05 ± 1.05 mm at -1 mm, 1.51 ± 0.89 mm at -3 mm, and 0.92 ± 0.7 mm at -5 mm. CG showed readings of 1.22 ± 1 at -1 mm, 0.92 ± 0.67 at -3 mm, and 0.73 ± 0.69 at -5 mm. In comparison to CG, SG showed a significant reduction in horizontal losses at -1 mm. Vertical crest dimensions decreased by 1.64 ± 1.11 mm for the buccal bone height and by 1.56 ± 1.08 mm for lingual bone height in SG; in CG, the buccal and lingual bone height had mean values of 2.08 ± 1.44 mm and 1.73 ± 1.27 mm, respectively. There was no statistically significant difference observed in the vertical losses between the groups. Conclusions: Following a period of 4 months, the PLGA scaffold was completely resorbed. Based on CBCT measurements, horizontal resorption was lower than CG at -1 mm coronally. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose (BNC) is a durable, flexible, and dynamic biomaterial capable of serving a wide variety of fields, sectors, and applications within biotechnology, healthcare, electronics, agriculture, fashion, and others. BNC is produced spontaneously in carbohydrate-rich bacterial culture media, forming a cellulosic pellicle via a nanonetwork of fibrils extruded from certain genera. Herein, we demonstrate engineering BNC-based scaffolds with tunable physical and mechanical properties through postprocessing. Human skeletal muscle myoblasts (HSMMs) were cultured on these scaffolds, and in vitro electrical stimulation was applied to promote cellular function for tissue engineering applications. We compared physiologic maturation markers of human skeletal muscle myoblast development using a 2.5-dimensional culture paradigm in fabricated BNC scaffolds, compared to two-dimensional (2D) controls. We demonstrate that the culture of human skeletal muscle myoblasts on BNC scaffolds developed under electrical stimulation produced highly aligned, physiologic morphology of human skeletal muscle myofibers compared to unstimulated BNC and standard 2D culture. Furthermore, we compared an array of metrics to assess the BNC scaffold in a rigorous head-to-head study with commercially available, clinically approved matrices, Kerecis Omega3 Wound Matrix (Marigen) and Phoenix as well as a gelatin methacryloyl (GelMA) hydrogel. The BNC scaffold outcompeted industry standard matrices as well as a 20% GelMA hydrogel in durability and sustained the support of human skeletal muscle myoblasts in vitro. This work offers a robust demonstration of BNC scaffold cytocompatibility with human skeletal muscle cells and sets the basis for future work in healthcare, bioengineering, and medical implant technological development.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.

Purpose: To compare bone substitutes composed of glycated collagen with synthetic micro-sized (1 to 10 µm) hydroxyapatite (OB) vs non-cross-linked collagen matrix with large-particle (250 to 1,000 µm) bovine-derived hydroxyapatite (BOC). Materials and Methods: The P1 to P4 premolars were bilaterally extracted from the mandibles of 19 Beagle dogs. After 21 days, osteotomies were created in each dog that received OB or BOC and were covered with a collagen membrane or were left untreated. The animals were randomly divided into three groups based on sacrifice time (4, 12, or 24 weeks). The right and left hemimandibles were trimmed to facilitate imaging and histology, and all tissues were placed in 10% neutral-buffered formalin. Microcomputed tomography (MicroCT 40 Scanner, Scanco) was used to analyze bone sections. Bone volume, residual material volume, and bone mineral density were determined for each treatment site (OB and BOC) based on a volume of interest that encompassed the original defect. Additionally, blinded histopathologic assessment (based on the ISO 10993-6 scoring system) and histomorphometry were performed on sections ground to < 100 µm thick and stained with Stevenel's blue. Results: No clinical side effects were noted. No statistical differences were observed for OB vs BOC regarding the mineral volume percentage. Compared to OB, BOC had significantly higher mean mineralization densities at 12 weeks (P < .01), but this difference did not extend to 24 weeks. For residual grafting material, bone maturation, alveolar ridge restoration, and inflammatory response, OB showed a residual amount of bone graft and no statistical differences compared to BOC. Conclusion: Both OB and BOC represent valid treatment options for critically sized bone defects. Both bone fillers outperformed the sham-operated, ungrafted (empty) control, demonstrating statistically improved bone growth and ridge restoration. [ABSTRACT FROM AUTHOR]

Bioceramics composed of calcium and magnesium silicates have garnered increasing attention for the development of porous scaffolds in bone tissue engineering (BTE). This heightened interest is primarily attributed to their remarkable bioactivity and their capacity to form strong bonds with hard tissue. Fabricating nanocomposite scaffolds is a recognized approach for improving the characteristics of scaffolds used in BTE. This research investigates the mechanical and biological properties, antibacterial activity, and drug-release characteristics of scaffolds composed of akermanite (AKT), monticellite (MON), and monticellite-akermanite (MON-AKT). These scaffolds were fabricated utilizing the space holder process. Additionally, the in vitro drug release profile and antimicrobial activity of Azithromycin (AZT)-loaded MON-AKT composite scaffolds were investigated. The findings showed that the Mon-15 wt% AKT nanocomposite scaffold had the highest density, the smallest grain and micropore sizes, and the lowest porosity. In contrast, integrating AKT into MON-based composite scaffolds resulted in materials characterized by high mechanical strength and stability within physiological environments. The MON-AKT nanocomposite scaffolds exhibited cytocompatibility and demonstrated a high level of alkaline phosphatase (ALP) activity in osteogenic studies. Furthermore, antimicrobial activity assessments revealed that the AZT-encapsulated MON-AKT composite scaffolds effectively inhibited the growth of both S. aureus and E. coli bacteria. The outcomes showed that the antibacterial efficacy of the scaffold depends on both the amount of AZT and the type of bacteria. Overall, MON-AKT/3AZT scaffolds exhibited significantly superior bacterial inhibition compared to other scaffolds, making it a promising option for treating bone tissue defects. [ABSTRACT FROM AUTHOR]

Nowadays, the utilization of 3D printing has become common in the construction of composite scaffolds. In this research, the co-precipitation method was applied to synthesize pure strontium hexaferrite oxide (SrFe 12 O 19) and magnesium-doped strontium hexaferrite oxide nanoparticles (Mg–SrFe 12 O 19). The synthesized SrFe 12 O 19 nanoparticles had a spherical morphology with a mean size of 60 nm and magnetization (Ms) value of 54.38 emu/g. The Mg–SrFe 12 O 19 also had a spherical morphology with a mean particle size of 46 nm and a magnetization value of 29.89 emu/g. The produced polycaprolactone composite scaffolds containing different amounts (0, 25, 50, and 75 wt%) of reinforcement were fabricated by the 3D robocasting printing method. Based on the results of the compression test, the 25 wt% addition of the pure SrFe 12 O 19 nanoparticles to the polycaprolactone scaffold increased the compressive strength from 2.87 to 11.68 MPa compared to the 100 wt% pure polycaprolactone scaffold. Furthermore, the polycaprolactone nanocomposite scaffold containing 25 wt% Mg–SrFe 12 O 19 also increased the compressive strength compared to the pure polycaprolactone scaffold to 12.94 MPa. Therefore, the 25 wt% reinforced scaffold was chosen as the optimal sample. The contact angles of the pure polycaprolactone SrFe 12 O 19 and Mg– SrFe 12 O 19 reinforced polycaprolactone scaffolds were 77.17, 68.53, and 35.58°, respectively. The values indicate the significant effect of doping magnesium on the wettability. The degradability of the 3D-printed scaffolds containing 25 wt% of the two different reinforcements was evaluated for 28 days immersing in phosphate-buffered saline (PBS) solution. The results revealed that the degradability was higher for the Mg–SrFe 12 O 19 after 28 days compared to the composite scaffold reinforced by pure SrFe 12 O 19 reinforcement. Moreover, it was shown that the bioactivity and cell adhesion of MG63 cells for the scaffolds reinforced by Mg–SrFe 12 O 19 have increased in laboratory conditions. Based on the MTT test, it was observed that both of the scaffolds were non-toxic. The results obtained in this study, suggest that polycaprolactone nanocomposite scaffolds containing 25 wt% of Mg–SrFe 12 O 19 , made by the 3D robocasting printing method, are suitable for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Cardiovascular disease such as myocardial infarction is one of the chief reasons for death universally. An extensive variety of natural and synthetic biodegradable polymers have been studied lately for cardiac tissue engineering applications. Cardiac tissue regeneration is a substitute approach for in situ cellular cardiomyoplasties, which is considered to renovate infarcted myocardium utilizing cells, scaffold, and growth factors. Polymer-based scaffolds including graphene and carbon nanotubes can be employed for heart tissue engineering. In this review, we consider the literature in terms of cardiac tissue engineering and discuss the most recent developments in terms of scaffold-based polymers for cardiac tissue regeneration. [ABSTRACT FROM AUTHOR]

[Display omitted] Low mechanical strength is still the key question for collagen hydrogel consisting of nanofibrils as hard tissue repair scaffolds with no loss of biological function. In this work, novel collagen nanofibrous hydrogels with high mechanical strength were fabricated based on the pre-protection of trisodium citrate masked Zr(SO 4) 2 solution for collagen self-assembling nanofibrils and then further coordination with Zr(SO 4) 2 solution. The mature collagen nanofibrils with d -period were observed in Zr(IV) mediated collagen hydrogels by AFM when the Zr(IV) concentration was ≥ 10 mmol/L, and the distribution of zirconium element was uniform. Due to the coordination of Zr(IV) with ─COOH, ─NH 2 and ─OH within collagen and the tighter entanglement of collagen nanofibrils, the elastic modulus and compressive strength of Zr(IV) mediated collagen nanofibrous hydrogel were 208.3 and 1103.0 kPa, which were approximate 77 and 12 times larger than those of pure collagen hydrogel, respectively. Moreover, the environmental stability such as thermostability, swelling ability and biodegradability got outstanding improvements and could be regulated by Zr(IV) concentration. Most importantly, the resultant hydrogel showed excellent biocompatibility and even accelerated cell proliferation. [ABSTRACT FROM AUTHOR]

This review underscores the novelty of silk sericin, often regarded as a byproduct in silk production. Comprising approximately 30% of silk, sericin possesses valuable properties that have been largely overlooked in favor of silk fibroin. This work focuses on innovative extraction methods to convert sericin, typically considered waste, into a valuable resource. By examining these extraction techniques alongside diverse applications, the review aims to enhance the recognition and utilization of silk sericin in research and industry. Various extraction processes where the traditional methods, and some new techniques, are all discussed. In detail, the advantages, limitations, and strategy optimization associated with each extraction method are highlighted. For instance, silk sericin has shown promise as a wound treatment agent, a scaffold for tissue engineering, a carrier for drug delivery, and a biomaterial for regenerative medicine in the field of biomedical science due to its biocompatibility, biodegradability, and nontoxicity. Additionally, it also finds application in the cosmetic industry, where it is used in skincare products due to its moisturizing, antioxidant, and antiaging properties. Eventually, the challenges, limitations, and prospects of silk sericin are intensively discussed. This comprehensive review is expected to serve the growing body of knowledge surrounding silk sericin and foster further research and development of silk sericin‐related fields. [ABSTRACT FROM AUTHOR]

In this work, five new peptides derived from natural resources and two peptide bolaamphiphiles were designed. The self-assembling ability of the peptides and the bolaamphiphiles, as well as their predicted antioxidant activity was examined computationally. In particular, replica modeling molecular dynamics studies were carried out at three different temperatures. Results showed that the bolaamphiphiles as well as three of the peptides efficiently formed spherical or fibrous assemblies, particularly at physiological temperatures. In addition, stacking interactions and hydrogen bonds played a critical role in assembly formation. Furthermore, molecular docking studies with extracellular matrix proteins such as the triple helix motif of collagen and the fibronectin (III) motif of tenascin-X displayed binding interactions with the peptides and the bolaamphiphiles. The most optimal peptide bolaamphiphile WMYGGGWMY-CO-NH-(CH2)4-YMWGGGYMW was then synthesized in the laboratory and its ability to form functional scaffolds upon binding to collagen and tenascin-X was examined. The scaffolds were bioprinted with co-cultures of fibroblasts and keratinocytes. The cells not only proliferated over time but also showed strong adherence and spreading within the matrix. Thus, the peptides and the bolaamphiphiles studied in this work, may be potentially developed as scaffold components for tissue regeneration applications. [ABSTRACT FROM AUTHOR]

3D printing of bio‐hydrogel scaffolds are widely used in tissue regeneration. However, due to the ultra‐soft properties of bio‐hydrogels, it is hard to print them precisely. Here, crystal transduction 3D printing with high fidelity is proposed to address this challenge. A phase‐transition bio‐inks system with beeswax is developed for crystal transduction, which can accelerate energy consumption and induce soft bio‐inks to quickly harden during printing. Interestingly, an interconnected porous hydrogel scaffold can be obtained after washing the crystal beeswax. The porous hydrogel scaffold demonstrated excellent biocompatibility and cell proliferation effect in vitro and is free from defense responses and immunogenicity in vivo. Muscle analog porous scaffolds constructed by high‐fidelity 3D printing significantly improve the tissue function recovery of rats with muscle defects, compared with the conventional printed hydrogel with a non‐matched shape. These structure‐performance design rules create exciting opportunities to customize 3D‐printed porous hydrogel scaffolds with high fidelity. [ABSTRACT FROM AUTHOR]

Hydrogels are regarded as ideal tissue scaffold materials owing to their unique advantages, but problems such as low strength and easy cracking have become bottlenecks that limit their practical applicability. Constructing reinforced hydrogels is a widely studied approach for performance enhancement. Therefore, herein, cellulose nanocrystals were introduced as reinforcement into a thermally responsive hydrogel matrix through a Schiff base, achieving a cellulose nanocrystal-reinforced thermally responsive dynamic hydrogel. The CNC-reinforced hydrogel was characterized in detail, and the influence of CNCs on hydrogel properties was systematically investigated. Moreover, the thermally responsive and dynamic properties of the resulting hydrogels were tested to evaluate their mechanical performance. This work provides a feasible solution for the design of hydrogel-based tissue scaffold materials with long service life. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) viscoelasticity broadly regulates cell behavior. While hydrogels can approximate the viscoelasticity of native ECM, it remains challenging to recapitulate the rapid stress relaxation observed in many tissues without limiting the mechanical stability of the hydrogel. Here, we develop macroporous alginate hydrogels that have an order of magnitude increase in the rate of stress relaxation as compared to bulk hydrogels. The increased rate of stress relaxation occurs across a wide range of polymer molecular weights (MWs), which enables the use of high MW polymer for improved mechanical stability of the hydrogel. The rate of stress relaxation in macroporous hydrogels depends on the volume fraction of pores and the concentration of bovine serum albumin, which is added to the hydrogels to stabilize the macroporous structure during gelation. Relative to cell spheroids encapsulated in bulk hydrogels, spheroids in macroporous hydrogels have a significantly larger area and smaller circularity because of increased cell migration. A computational model provides a framework for the relationship between the macroporous architecture and morphogenesis of encapsulated spheroids that is consistent with experimental observations. Taken together, these findings elucidate the relationship between macroporous hydrogel architecture and stress relaxation and help to inform the design of macroporous hydrogels for materials-based cell therapies. [ABSTRACT FROM AUTHOR]

Many withered leaves or flowers spontaneously curl and transform from flattened structures into tubular constructs upon dehydration. Inspired by this phenomenon, an innovative strategy is developed to design stimuli‐responsive scaffolds that are capable of programmable transformation from flattened 2D constructs into various curled 3D tissue‐mimicking structures. Specifically, Janus‐structured scaffolds consisting of a passive layer of polycaprolactone and an active, triggered‐transforming layer of methacrylate gelatin/alginate hydrogel are 3D‐printed, which replicate the asymmetrical structure of leaves and enabled on‐demand transformation into desired curvatures and shapes through mimicking the regulation mechanism of leaves curling behavior by mesophyll matrix stiffness and vein patterns. Particularly for vascular reconstruction, multi‐step transformation scaffolds capable of primary 2D‐to‐3D transformation into tubular constructs induced by dehydration, and secondary transformation to adapt to the local intravascular geometry in vivo, are successfully developed. In addition, the oriented polycaprolactone layer of the printed scaffold can enable the adhesion, proliferation, and orientation of endothelial cells, thus demonstrating a novel strategy for the design of tissue‐engineered blood vessels. In general, this study provides an innovative design strategy for programmable biomaterials capable of shape morphing and adaptation in physiological conditions, thereby opening up a new avenue for the design of intelligent biomaterials in regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the therapeutic effects and mechanisms of PRP-exos combined with cyclic peptide-modified β-TCP scaffold in the treatment of rabbit knee cartilage defect. Methods: PRP-exos were extracted and characterized by TEM, NTA and WB. The therapeutic effects were evaluated by ICRS score, HE staining, Immunohistochemistry, qRT-PCR and ELISA. The repair mechanism of PRP-exos was estimated and predicted by miRNA sequencing analysis and protein–protein interaction network analysis. Results: The results showed that PRP-exos had a reasonable size distribution and exhibited typical exosome morphology. The combination of PRP-exos and cyclic peptide-modified β-TCP scaffold improved ICRS score and the expression level of COL-2, RUNX2, and SOX9. Moreover, this combination therapy reduced the level of MMP-3, TNF-α, IL-1β, and IL-6, while increasing the level of TIMP-1. In PRP-exos miRNA sequencing analysis, the total number of known miRNAs aligned across all samples was 252, and a total of 91 differentially expressed miRNAs were detected. The results of KEGG enrichment analysis and the protein–protein interaction network analysis indicated that the PI3K/AKT signaling pathway could impact the function of chondrocytes by regulating key transcription factors to repair cartilage defect. Conclusion: PRP-exos combined with cyclic peptide-modified β-TCP scaffold effectively promoted cartilage repair and improved chondrocyte function in rabbit knee cartilage defect. Based on the analysis and prediction of PRP-exos miRNAs sequencing, PI3K/AKT signaling pathway may contribute to the therapeutic effect. These findings provide experimental evidence for the application of PRP-exos in the treatment of cartilage defect. [ABSTRACT FROM AUTHOR]

This review explores core‐shell scaffolds in bone tissue engineering, highlighting their osteoconductive and osteoinductive properties critical for bone growth and regeneration. Key design factors include material selection, porosity, mechanical strength, biodegradation kinetics, and bioactivity. Electrospun core‐shell nanofibrous scaffolds demonstrate potential in delivering therapeutic agents and enhancing bone regeneration. Critical characterization techniques include structural, surface, chemical composition, mechanical, and degradation analyses. Scaling up production poses challenges, addressed by innovative electrospinning techniques. Future research focuses on regulatory and commercial considerations, while exploring advanced materials and fabrication methods to optimize scaffold performance for improved clinical outcomes. [ABSTRACT FROM AUTHOR]

In this study, zinc silicate hybrid scaffolds with hierarchical meso/macroporous structures were synthesized using evaporation-induced self-assembly and sacrificial foamy templates. F127 triblock copolymer and polyurethane (PU) foam served as templates for mesoporosity and macroporosity, respectively. The scaffolds were calcined at 550, 650, and 750 °C for 2 h to remove the templates and form the crystalline phase. Analytical techniques, including BET, XRD, SEM, FTIR, and STA, were used to study the impact of calcination temperature on the scaffolds' meso-texture and crystalline phase. Results showed that increasing the calcination temperature to 750 °C significantly enhanced the overall crystallinity. The crystallized ZnO content increased from 10.3 wt% to 32 wt%, and the willemite (Zn 2 SiO 4) crystalline phase formed. Willemite content was approximately 3 wt% at 650 °C and 67 wt% at 750 °C, as determined by quantitative XRD analyses via Rietveld refinement. The emergence of the willemite phase adversely impacted the specific surface area, leading to a reduction from 123.18 m2/g to 2.18 m2/g, and compromised meso-texture-related characteristics, indicating a substantial disruption in mesoporosity. The pure willemite sample was also obtained by increasing the calcination temperature up to 1000 °C. Although the sample contained no secondary phase, the specific surface area and total mesopore volume were drastically reduced, indicating the negative effect of high calcination temperature on mesoporosity. In contrast to the mesostructure, the macrostructure of the scaffolds exhibited negligible sensitivity to calcination temperature, maintaining a mean macropore diameter of around 200 μm. Furthermore, the in vitro performance of the scaffolds was evaluated by assessing apatite formation ability, degradability, and cytocompatibility. It was demonstrated that the scaffolds calcined at 750 °C exhibited superior performance in terms of apatite formation and cytocompatibility when cultivated with MG-63 human osteosarcoma cells. [ABSTRACT FROM AUTHOR]

Introduction: Pore structure and geometry are crucial in scaffold development for tissue engineering. From this viewpoint, pore geometry characterization methods will aid in understanding the influence of pore structure (pore size and diffusivity) on its properties. These properties determine how oxygen and water enter the scaffold, forming adsorption states. Previous studies showed that the addition of graphene (G) to polycaprolactone (PCL) increased the pore size, and played a significant role in tissue regeneration. Therefore, this study aimed to evaluate pore structure, geometry, and viability that are suitable for osteogenesis. Materials and methods: Morphology, size, and size distribution of PCL and PCL/G scaffolds were measured at concentrations of 1, 2, and 3 wt% G for the pore structure, while the connectivity of the scaffold's pore was analyzed using the geodesic tortuosity. This is essential because these factors promote the viability of osteogenesis-supporting cells. Results and discussion: The results showed that 3 wt% G had a good water diffusivity rate, larger pores, better connectivity, and viability than other concentrations. Conclusion: In conclusion, the presence of G in scaffolds affects the pore geometry and structure. This results in several advantageous effects that support osteogenesis, such as increased water and nutrient uptake, enhanced waste metabolism transport, and increased viability of the cells. [ABSTRACT FROM AUTHOR]

Various studies have been carried out on renewable materials obtained from different natural resources and explored their applicability for multiple fields including biomedical. Among them, polysaccharides and polypeptides as alternatives to petroleum-based raw materials have attracted considerable attention because of their cost-effective, biocompatible, biodegradable, and eco-friendly, as well as their antimicrobial properties. Furthermore, the incorporation of these biobased materials in the formulation of polymeric materials could be advantageous. Recently, research on utilization of these biobased materials for the creation of nanocomposites of hydrogels (NCHs) has become a hotspot in the biomedical field. They have also paved the way for their uses in research for both in vivo and in vitro applications. Initially, in this review, we have briefly summarized the employment of biobased materials as well as different reinforcing materials in the formulation of biobased NCHs. We have also discussed their utilization as scaffolds for tissue engineering, carriers for drug delivery, material for wound dressing as well as biosensing and so on. Finally, we demonstrated the prospects and challenges associated with these materials, in order to deliver important information to produce biobased NCHs with desired properties for biomedical applications. [ABSTRACT FROM AUTHOR]

Poly(2-hydroxyethyl methacrylate) (PHEMA) has been widely used in medical materials for several decades. However, the poor mechanical properties of this material have limited its application in the field of tissue engineering. The purpose of this study was to fabricate a scaffold with suitable mechanical properties and in vitro cell responses for soft tissue by using poly(HEMA-co-MMA) with various concentration ratios of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). To customize the concentration ratio of HEMA and MMA, the characteristics of the fabricated scaffold with various concentration ratios were investigated through structural morphology, FT-IR, mechanical property, and contact angle analyses. Moreover, in vitro cell responses were observed according to the various concentration ratios of HEMA and MMA. Consequently, various morphologies and pore sizes were observed by changing the HEMA and MMA ratio. The mechanical properties and contact angle of the fabricated scaffolds were measured according to the HEMA and MMA concentration ratio. The results were as follows: compressive maximum stress: 254.24–932.42 KPa; tensile maximum stress: 4.37–30.64 KPa; compressive modulus: 16.14–38.80 KPa; tensile modulus: 0.5–2 KPa; and contact angle: 36.89–74.74°. In terms of the in vitro cell response, the suitable cell adhesion and proliferation of human dermal fibroblast (HDF) cells were observed in the whole scaffold. Therefore, a synthetic hydrogel scaffold with enhanced mechanical properties and suitable fibroblast cell responses could be easily fabricated for use with soft tissue using a specific HEMA and MMA concentration ratio. [ABSTRACT FROM AUTHOR]

Introduction: Natural biopolymers are used for various purposes in healthcare, such as tissue engineering, drug delivery, and wound healing. Bacterial cellulose and chitosan were preferred in this study due to their non-cytotoxic, biodegradable, biocompatible, and non-inflammatory properties. The study reports the development of a magnetic bacterial cellulose-chitosan (BC-CS-Fe3O4) nanocomposite that can be used as a biocompatible scaffold for tissue engineering. Iron oxide nanoparticles were included in the composite to provide superparamagnetic properties that are useful in a variety of applications, including osteogenic differentiation, magnetic imaging, drug delivery, and thermal induction for cancer treatment. Methods: The magnetic nanocomposite was prepared by immersing Fe3O4 in a mixture of bacterial cellulose-chitosan scaffold and then freeze-drying it. The resulting nanocomposite was characterized using FE-SEM and FTIR techniques. The swelling ratio and mechanical strength of the scaffolds were evaluated experimentally. The biodegradability of the scaffolds was assessed using PBS for 8 weeks at 37°C. The cytotoxicity and osteogenic differentiation of the nanocomposite were studied using human adipose-derived mesenchymal stem cells (ADSCs) and alizarin red staining. One-way ANOVA with Tukey's multiple comparisons test was used for statistical analysis. Results: The FTIR spectra demonstrated the formation of bonds between functional groups of nanoparticles. FE-SEM images showed the integrity of the fibrillar network. The magnetic nanocomposite has the highest swelling ratio (2445% ± 23.34) and tensile strength (5.08 MPa). After 8 weeks, the biodegradation ratios of BC, BC-CS, and BC-CS-Fe3O4 scaffolds were 0.75% ± 0.35, 2.5% ± 0.1, and 9.5% ± 0.7, respectively. Magnetic nanocomposites have low toxicity (P < 0.0001) and higher osteogenic potential compared to other scaffolds. Conclusion: Based on its high tensile strength, low water absorption, suitable degradability, low cytotoxicity, and high ability to induce an increase in calcium deposits by stem cells, the magnetic BC-CS-Fe3O4 nanocomposite scaffold can be a suitable candidate as a biomaterial for osteogenic differentiation. [ABSTRACT FROM AUTHOR]

Strontium is a potent osteo-stimulative element with a wide safe dosage range. In this work, calcium-strontium phosphate (Ca 2 Sr(PO 4) 2 ; abbreviation: CSP) was synthesized, and 3D-printed CSP-based composite (CSP-T) ceramic scaffolds were prepared by introduction of β-tricalcium phosphate (TCP). When sintering the CSP-T ceramic scaffolds, no new phase was produced, but the strontium from CSP was substituted for calcium in TCP; the TCP additives promoted densification of scaffold filaments, resulting in lower porosity of the CSP-T ceramic scaffolds. The porosity (25.6%–77.1 %) and compressive strength (1.5–44.5 MPa) of CSP-T ceramic scaffolds could be adjusted by altering the amount of TCP additives and the sintering temperature. The CSP-T ceramic scaffolds gradually released ions of calcium, phosphorus and strontium, which were in favor of cell growth and osteogenic differentiation. The CSP-T ceramic scaffolds modified by 25 wt% TCP possessed the greatest performances on enhancing mechanical strength and cellular response, which let them serve as promising bone grafts to treat various sites of bone defects. [ABSTRACT FROM AUTHOR]

There has been an important interest in to use of electrospun nanomaterials for tissue engineering applications due to the excellent scaffold-cell interaction provided by high interconnectivity and high porosity by electrospun nanofibers. In this study, Polyacrylonitrile (PAN) and carbon nanotube-inserted PAN (PAN/CNT) nanofibers were produced by the electrospinning method and characterized by SEM, FT-IR, and EIS spectroscopy. Both PAN and PAN/CNT nanofibers were obtained beadless and ordered with the average fiber diameters of 277.61 ± 43.6 and 171.01 ± 48.4, respectively. The influence of CNT addition on PAN nanofibers was observed with the decrease of diameter and increase of electrical conductivity of nanofibers. Then, the biocompatibility of PAN and PAN/CNT nanofibers was evaluated by the MTT and AO/EB double-staining experiments. It was observed that the nanofibers showed no cytotoxic effect on L929 fibroblast cells. In the docking experiments, while both PAN and PAN/CNT showed energetically favorable interactions (ΔG = −4.60 kcal/mol; −7.26 kcal/mol, respectively) with the membrane bilayer complex, PAN/CNT formed a more stable binding with the cellular membrane compared to PAN alone. Docking results mechanistically support the more effective increase in the proliferation of L929 fibroblasts at high concentrations in vitro, as PAN/CNT exhibits stronger binding affinity and interaction with the cellular membrane. The increase in electrical conductivity of nanofibers influenced the proliferation positively, as well. [ABSTRACT FROM AUTHOR]

Gelatin methacrylate (GelMA) is a photo-cross-linkable biopolymer. A combination of GelMA with biodegradable polyesters such as PCL (poly‐ε‐caprolactone) and their triblock derivatives improve the mechanical properties of GelMA. PCL-PEG-PCL (PCEC) was synthesized using ring-opening polymerization of ε-caprolactone in the presence of polyethylene glycol (PEG). The GelMA- PCEC was fabricated using freeze-drying and 3D printing and their porosity, mechanical properties, and swelling behavior were investigated. Human dental pulp stem cells were cultured on the scaffolds for a period of 14 days and cell adhesion was evaluated by scanning electron microscopy. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by Alizarin red S. Results showed that the 3D-printed scaffold had higher water absorption rate, retaining its structure up to a strain of 0.2 %, and a higher Young's modulus compared to the freeze-dried scaffold. In terms of cell viability, the 3D-printed scaffold outperformed the freeze-dried scaffold with a percentage of 86 % and 63 % viability respectively. Moreover, the 3D-printed scaffold exhibited better osteodifferentiation with calcium deposition. Overall, these findings suggest that the 3D-printed scaffold may have advantages over the freeze-dried scaffold in tissue engineering applications that require high water absorption, elasticity, and cell viability. The fabricated scaffolds provided suitable cell proliferation. [ABSTRACT FROM AUTHOR]

3D‐printed biomaterial implants are revolutionizing personalized medicine for tissue repair, especially in orthopedics. In this study, a radiopaque bismuth oxide (Bi2O3) doped polycaprolactone (PCL) composite is developed and implemented to enable the use of diagnostic X‐ray technologies, especially spectral photon counting X‐ray computed tomography (SPCCT), for comprehensive tissue engineering scaffold (TES) monitoring. PCL filament with homogeneous Bi2O3 nanoparticle (NP) dispersion (0.8 to 11.7 wt%) is first fabricated. TES are then 3D printed with the composite filament, optimizing printing parameters for small features and severely overhung geometries. These composite TES are characterized via micro‐computed tomography (µCT), tensile testing, and a cytocompatibility study, with 2 wt% Bi2O3 NPs providing improved tensile properties, equivalent cytocompatibility to neat PCL, and excellent radiographic distinguishability. Radiographic performance is validated in situ by imaging 4 and 7 wt% Bi2O3 doped PCL TES in a mouse model with µCT, showing excellent agreement with in vitro measurements. Subsequently, CT image‐derived swine menisci are 3D printed with composite filament and re‐implanted in corresponding swine legs ex vivo. Re‐imaging the swine legs via clinical CT allows facile identification of device location and alignment. Finally, the emergent technology of SPCCT unambiguously distinguishes the implanted meniscus in situ via color K‐edge imaging. [ABSTRACT FROM AUTHOR]

Biodegradable tissue engineering scaffolds have garnered increasing interest for their role in providing mechanical support, promoting tissue regeneration, and eliminating the need for removal. However, the in vivo degradation processes remain challenging to track. Here, a novel biodegradable polymer, N‐methyldiethanolamine (MDEA) and Gadolinium(III) diethylenetriamine pentaacetate (Gd‐DTPA) modified biodegradable photoluminescent polymers (BPLPMGd), which combines near‐infrared (NIR) fluorescence and magnetic resonance (MR) dual‐modality imaging are introduced to monitor scaffold degradation in vivo. The chemical structure of BPLPMGd is characterized and its dual‐imaging properties in vitro are evaluated. Subsequently, non‐invasive dual‐modality imaging to track the degradation of implanted BPLPMGd scaffolds is performed in a rat model, comparing these results with histological data. This approach reveals that BPLPMGd enables reliable non‐invasive tracking of the degradation, where NIR fluorescence imaging offers a qualitative and quantitative analysis of scaffold mass loss, total volume and solid content changes, while magnetic resonance imaging (MRI) details structural and morphological changes, allowing for 5D monitoring of implant degradation, including 3D structure, location, mass, volume, and geometry. The combination of these imaging modalities provides a comprehensive view of scaffold degradation, where the synergistic use of both yields results greater than either modality alone, offering unprecedented 5D information of implantable devices. This innovative approach has potential applications in regenerative engineering and beyond. [ABSTRACT FROM AUTHOR]

Highlights The mechanical strength of polylactic acid (PLA) can be improved by carbon fiber (CF) compositing to expand its application in tissue engineering scaffolds. However, the mechanical strength of CF‐reinforced polylactic acid (CFRPLA) composites is compromised due to weak interfacial interaction resulting from the chemically inert surface of CF. In the article, carbon nanotube (CNT) with poly(diallyldimethylammonium chloride) (PDDA) as a coupling agent was covered on CF to improve the chemical activity and roughness of the surface of CF, and then the as‐prepared CF‐PCNT were further incorporated into PLA via melt compounding. The yield strength, modulus, and thermal conductivity of PLA/CF‐PCNT were 14.09%, 7.65%, and 5.24% higher than those of PLA/CF, respectively, and the volume resistivity was 99.74% lower at a 10 wt% loading. The enhancement for the mechanical properties of PLA/CF‐PCNT composites could be ascribed to the mechanical locking, hydrogen bonds and covalent bonds between CF and matrix through the interface modulation of CNT and PDDA. This facile and non‐destructive method offers a novel strategy for the modification of CF fillers. CF was modified by PDDA and CNT through a facile and non‐destructive method. The active functional groups and roughness on the surface of CF were increased. The surfaces of CFs were characterized by FT‐IR, Raman spectra, XPS and SEM. The interface was improved by mechanical locking, covalent, and hydrogen bonds. The mechanical strength, electrical and thermal conductivity of composites were improved. [ABSTRACT FROM AUTHOR]

Addressing a critical challenge in current tissue-engineering practices, this study aims to enhance vascularization in 3D porous scaffolds by incorporating bioceramics laden with pro-angiogenic ions. Specifically, freeze-dried gelatin-based scaffolds were infused with sol-gel-derived powders of Cu-doped akermanite (Ca 2 MgSi2O 7) and bredigite (Ca 7 MgSi 4 O 16) at various concentrations (10, 20, and 30 wt%). The scaffolds were initially characterized for their structural integrity, biodegradability, swelling behavior, impact on physiological pH, and cytocompatibility with human umbilical vein endothelial cells (HUVECs). The silicate incorporation effectiveness in promoting vascularity was then assessed through HUVEC attachment, capillary tube formation, and ex-ovo chick embryo chorioallantoic membrane assays. The findings revealed significant improvements in both in-vitro and ex-ovo vascularity of the gelatin scaffolds upon the addition of Cu-doped akermanite. The most effective concentrations were determined to be 10 and 20 %, which led to notable HUVEC metabolic activity, a well-spread morphology with extensive peripheral filopodia and lamellipodia at 10 % and a cobblestone phenotype indicative of in-vivo endothelium at 20 % during cell attachment, the formation of complex networks of tubular structures, and robust vascularization in chick embryo development. Moving forward, the incorporation of Cu-doped akermanite into tissue-engineering scaffolds shows great potential for addressing the limitations of vascularization, especially for critical-sized bone defects, by facilitating the controlled release of pro-angiogenic and pro-osteogenic ions. [ABSTRACT FROM AUTHOR]

Due to their biocompatibility and wear resistance, ceramic materials have gained significant attention as excellent options to meet the growing demand for scaffolds in bone-defect treatment. However, current ceramic materials suffer from high hardness and unfavorable structure for the flow of body fluids, thus requiring the design of porous scaffolds. In this study, β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), and 45S5 Bioglass® (BG) were selected to prepare scaffolds with the gyroid structure using digital light processing (DLP) technology. Then the scaffolds' surface, structure, mechanical properties, and biological performance were characterized. The results verified that gyroid structures with different porosity could be well tailored by adjusting the original functions, meanwhile the details of the models were preserved during the DLP printing and sintering process. In addition, different shrinkage patterns were observed, with microscale shrinkage being larger than macroscale shrinkage. There was an excessive increase in the material width after the curing process, but the structure thickness decreased during the sintering phase. Notably, the elastic modulus increased as the porosity of the scaffold decreased. During the sintering process, the BG underwent crystallization reactions, while the HA experienced decomposition. In vitro experiments demonstrated that the scaffolds exhibited no toxicity and displayed excellent biocompatibility, making them suitable for cell growth and adhesion. And the ability of the scaffolds to promote cell proliferation and osteogenic differentiation was better with the increase in porosity. Besides, the newly formed bone tissue within the scaffold exhibited characteristics similar to cortical bone, both after 3 and 6 months in vivo. This study showed that the gyroid scaffold with high porosity (65.67 %) has a remarkable capacity to promote cortical bone healing and holds great promises in the future treatment of bone defects. [ABSTRACT FROM AUTHOR]

Regeneration of soft tissues, especially those requiring complex vascularization, is a major challenge in the field of tissue engineering. The current types of tissue engineering scaffolds include sponges, electric spinning silk, hydrogels, and 3D printed biomaterials. Among them, hydrogels have the unique property of mimicking extracellular matrix (ECM), which can provide a relatively stable microenvironment for cellular activities and facilitate cell adhesion, proliferation, and differentiation; thus, have become a promising scaffold. In this paper, we present a review of the commonly used types of natural hydrogels and their applications as scaffolds in tissue vascularization. First, we enumerate the importance and advantages of several types of commonly used hydrogels of natural origin in terms of fabricating vascularized tissues or organs. Second, we discuss two different formation modalities of blood vessels, as well as natural hydrogel-based vascularization strategies, including carrying growth factors, stem cell delivery, special scaffold structures and pharmaceutical-enhanced strategy. In addition, we describe the crosslinking strategies of hydrogels as scaffolds for regeneration of vascularized soft tissues, as well as the factors affecting it. Finally, new insights are provided for the development of natural hydrogel-based vascularized soft tissue regeneration research. [ABSTRACT FROM AUTHOR]

Bone defect is a common clinical orthopedic disease. The trend in this field is to develop tissue engineering scaffolds with appropriately designed components and structures for bone repair. Herein, inspired by the organic and inorganic components of bone matrix and the natural biomineralization mechanism, a MgSiO3@Fe3O4 nanoparticle composite polycaprolactone (PCL) hybrid mineralized scaffold for bone repair is developed by microfluidic 3D printing. The incorporation of MgSiO3@Fe3O4 within the PCL scaffold can effectively improve the bioactivity. In addition, a biomimetic mineralized layer is prepared on the surface of the scaffold, which endowed it with unique microstructural characteristics, enhanced cell adhesion and osteogenic activity, and thus improved the bone repair performance. Owing to these advantages, both in vivo and in vitro experiments have demonstrated that the designed scaffold has outstanding biocompatibility and bone repair performance. These features indicate that the organic–inorganic biomineralized hybrid scaffold can be a potential bone graft substitute for clinical bone repair. [ABSTRACT FROM AUTHOR]

Background: The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect. Methods: In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained. Results: The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet ß-cells was increased, and the maturity of the new islet ß-cells was increased. The immunogenicity of new islet ß-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site. Conclusions: New islet ß-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect. [ABSTRACT FROM AUTHOR]

Background: The use of biological scaffolds in regenerative endodontics has gained much attention in recent years. The search for a new biomimetic scaffold that contains tissue-specific cell homing factors could lead to more predictable tissue regeneration. The aim of this study was to prepare and characterize decellularized bovine dental pulp-derived extracellular matrix (P-ECM) hydrogels for regenerative endodontic applications. Methods: Freshly extracted bovine molar teeth were collected. Bovine dental pulp tissues were harvested, and stored at -40º C. For decellularization, a 5-day protocol was implemented incorporating trypsin/EDTA, deionized water and DNase treatment. Decellularization was evaluated by DNA quantification and histological examination to assess collagen and glycosaminoglycans (GAGs) content. This was followed by the preparation of P-ECM hydrogel alone or combined with hyaluronic acid gel (P-ECM + HA). The fabricated scaffolds were then characterized using protein quantification, hydrogel topology and porosity, biodegradability, and growth factor content using Enzyme-linked immunosorbent assay (ELISA): transforming growth factor beta-1(TGF-β1), basic fibroblast growth factor (bFGF), bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). Results: Decellularization was histologically confirmed, and DNA content was below (50 ng/mg tissue). P-ECM hydrogel was prepared with a final ECM concentration of 3.00 mg/ml while P-ECM + HA hydrogel was prepared with a final ECM concentration of 1.5 mg/ml. Total protein content in P-ECM hydrogel was found to be (439.0 ± 123.4 µg/µl). P-ECM + HA showed sustained protein release while the P-ECM group showed gradual decreasing release. Degradation was higher in P-ECM + HA which had a significantly larger fiber diameter, while P-ECM had a larger pore area percentage. ELISA confirmed the retention and release of growth factors where P-ECM hydrogel had higher BMP-2 release, while P-ECM + HA had higher release of TGF-β1, bFGF, and VEGF. Conclusions: Both P-ECM and P-ECM + HA retained their bioactive properties demonstrating a potential role as functionalized scaffolds for regenerative endodontic procedures. [ABSTRACT FROM AUTHOR]

Chondrocytes, the resident cells of articular cartilage, play a vital role in tissue maintenance and regeneration. Recent studies have highlighted chondrocyte senescence as a key contributor to cartilage dysfunction. In this study, we investigated the influence of substrate stiffness on chondrocyte senescence using polydimethylsiloxane (PDMS) substrates with varying stiffness ratios (1:5, 1:20, and 1:60). After culturing chondrocytes on these substrates, we found that softer substrates (1:60) significantly reduced chondrocyte senescence, as evidenced by a decrease in senescence‐associated β‐galactosidase (SA‐β‐gal) activity by 33% compared with stiffer substrates (1:5). Furthermore, quantitative real‐time polymerase chain reaction (PCR) analysis revealed that chondrocytes cultured on softer substrates exhibited lower expression levels of senescence‐related genes (e.g., p16INK4a) and matrix‐degrading enzymes (e.g., MMP13). These findings suggest that substrate stiffness plays a critical role in regulating chondrocyte senescence and could potentially inform the design of scaffolds for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

The most common technologies in tissue engineering include growth factor therapies; metal implants, such as titanium; 3D bioprinting; nanoimprinting for ceramic/polymer scaffolds; and cell therapies, such as mesenchymal stem cells (MSCs). Cell therapy is a promising alternative to organ grafts and transplants in the treatment of numerous musculoskeletal diseases. MSCs have increasingly been used in generative medicine due to their specialized self‐renewal, immunomodulation, multiplication, and differentiation properties. To further expand the potential of these cells in tissue repair, significant efforts are currently dedicated to the production of biomaterials with desirable short‐ and long‐term biophysical properties that can aid the differentiation and expansion of MSCs. Biomaterials support MSC differentiation by modulating their characteristics, such as composition, mechanical properties, porosity, and topography. This review aimed to describe recent MSC approaches, including those associated with biomaterials, from experimental, clinical, and preclinical studies with sheep models. [ABSTRACT FROM AUTHOR]

Biological and mechanical mismatches between engineered scaffolds and native tissues poses widespread challenges for tissue restoration. Native‐like anisotropy is a critical characteristic for functional tissue replacements, yet it is an often‐overlooked aspect when designing new scaffolds. In this study, fiber‐reinforced tubular scaffolds are developed, mimicking the anisotropic characteristics of natural tissues, using native‐like silk fibroin. To predict the mechanical behavior of these innovative scaffolds, a mathematical model is employed, utilizing the properties of the scaffolds’ constituent materials, and experimentally validated through tensile testing. This approach addresses significant challenges in the design of new scaffold implants by enabling to efficiently predict the performance of several configurations, narrowing down the experimental research space. The proposed platform constitutes an appealing tool for the development of clinically relevant tissue‐equivalents. [ABSTRACT FROM AUTHOR]

Extrusion‐based 3D printing technology is currently demonstrating considerable potential in the field of tissue engineering scaffolds, enabling the construction of in vitro models with complex structures and functions using a wide range of biomaterials and cells at a low cost. In recent years, researchers have spent considerable effort developing novel bio‐inks and employing a greater variety of cell sources to enhance biological compatibility and functionality. However, the majority of current bio‐ink materials are unprintable due to their low viscosity and long curing time, as well as insufficient shape fidelity before the secondary cross‐linking process. The study aims to bridge this gap by optimizing the material ratios and predicting the printing process before work. This article presents new strategies for the design, fabrication, and analysis of a new composite bio‐ink material. The optimal ink ratios are verified by a design of experiments (DOE) experimental design and evaluation metrics for printing printability (Pr) values. A machine learning model is used to predict the ink printing area and determine the printing process parameters. The influence mechanism of ink materials with different concentrations of poly (ethylene glycol) diacrylate (PEGDA) ratios on printed fibers is investigated. Finally, the optimal results are used as an example to demonstrate the printability of multilayer stents. Thus, the design approach allows for the rapid and cost‐effective exploration of novel ink ratios, while also providing higher fidelity and more accurate process metrics for the fabrication of tissue structures with multidimensional variables. [ABSTRACT FROM AUTHOR]

The development of injectable hydrogels for soft tissue regeneration has gained significant attention due to their minimally invasive application and ability to conform precisely to the shape of irregular tissue cavities. This study presents a novel injectable porous scaffold based on natural polymers that undergoes in situ crosslinking, forming a highly resilient hydrogel with tailorable mechanical and physical properties to meet the specific demands of soft tissue repair. By adjusting the formulation, we achieved a range of stiffness values that closely mimic the mechanical characteristics of native tissues while maintaining very high resilience (>90%). The effects of gelatin, alginate, and crosslinker concentrations, as well as porosity, on the hydrogel's properties were elucidated. The main results indicated a compression modulus range of 2.7–89 kPa, which fits all soft tissues, and gelation times ranging from 5 to 30 s, which enable the scaffold to be successfully used in various operations. An increase in gelatin and crosslinker concentrations results in a higher modulus and lower gelation time, i.e., a stiffer hydrogel that is created in a shorter time. In vitro cell viability tests on human fibroblasts were performed and indicated high biocompatibility. Our findings demonstrate that these injectable hydrogel scaffolds offer a promising solution for enhancing soft tissue repair and regeneration, providing a customizable and resilient framework that is expected to support tissue integration and healing with minimal surgical intervention. [ABSTRACT FROM AUTHOR]

Tissue engineering has great potential for the restoration of damaged tissue due to injury or disease. During tissue development, scaffolds provide structural support for cell growth. To grow healthy tissue, the principal components of such scaffolds must be biocompatible and nontoxic. Poly(ε-caprolactone) (PCL) is a biopolymer that has been used as a key component of composite scaffolds for tissue engineering applications due to its mechanical strength and biodegradability. However, PCL alone can have low cell adherence and wettability. Blends of biomaterials can be incorporated to achieve synergistic scaffold properties for tissue engineering. Electrospun PCL-based scaffolds consist of single or blended-composition nanofibers and nanofibers with multi-layered internal architectures (i.e., core-shell nanofibers or multi-layered nanofibers). Nanofiber diameter, composition, and mechanical properties, biocompatibility, and drug-loading capacity are among the tunable properties of electrospun PCL-based scaffolds. Scaffold properties including wettability, mechanical strength, and biocompatibility have been further enhanced with scaffold layering, surface modification, and coating techniques. In this article, we review nanofibrous electrospun PCL-based scaffold fabrication and the applications of PCL-based scaffolds in tissue engineering as reported in the recent literature. [ABSTRACT FROM AUTHOR]

Schematic illustration showing the process of creating conductive MOF-coated 3D-printed scaffolds and their use in the treatment of osteosarcoma and for aiding in bone repair. [Display omitted] The integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal–organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). A tunable thickness of Cu-HHTP cMOF on PCL scaffolds was achieved via the alternative deposition of metal ions and HHTP. The resulting composite PCL@Cu-HHTP scaffolds not only demonstrated potent photothermal conversion capability for efficient OS ablation but also promoted the bone repair process by virtue of their cell-friendly hydrophilic interfaces. Therefore, the cMOF-engineered dual-functional 3D-printing scaffolds show promising potential for treating bone tumors by offering sequential anti-tumor effects and bone regeneration capabilities. This work also presents a new avenue for the interface engineering of bioactive scaffolds to meet multifaceted demands in osteosarcoma-related bone defects. [ABSTRACT FROM AUTHOR]

The liver coordinates over 500 biochemical processes crucial for maintaining homeostasis, detoxification, and metabolism. Its specialized cells, arranged in hexagonal lobules, enable it to function as a highly efficient metabolic engine. However, diseases such as cirrhosis, fatty liver disease, and hepatitis present significant global health challenges. Traditional drug development is expensive and often ineffective at predicting human responses, driving interest in advanced in vitro liver models utilizing 3D bioprinting and microfluidics. These models strive to mimic the liver's complex microenvironment, improving drug screening and disease research. Despite its resilience, the liver is vulnerable to chronic illnesses, injuries, and cancers, leading to millions of deaths annually. Organ shortages hinder liver transplantation, highlighting the need for alternative treatments. Tissue engineering, employing polymer-based scaffolds and 3D bioprinting, shows promise. This review examines these innovative strategies, including liver organoids and liver tissue-on-chip technologies, to address the challenges of liver diseases. [ABSTRACT FROM AUTHOR]

Craniofacial bone defects result from various disorders such as trauma, congenital malformations and infections. Cleft lip and palate are the most prevalent congenital craniofacial birth defect in humans. Growth factors (GFs) are soluble proteins secreted by cells that regulate various cellular processes and tissue regeneration. At present, developing three-dimensional scaffolds for delivering GFs to the site of injury has become an important aspect in craniofacial bone regeneration. This study aims to develop a novel 3D bone substitute using lyophilized-platelet-rich fibrin (LyPRF) biocomposite scaffolds for potential application for CLP repair. Collagen (C), bioglass (BG), and LyPRF were used to fabricate a biocomposite (C-BG-LyPRF) scaffold. The physical, chemical, and biocompatibility properties of the scaffold were evaluated. The C-BG-LyPRF scaffold demonstrated a mean pore diameter of 146 µm within a porosity of 87.26%. The FTIR spectra verified the presence of am-ide I, II, and III functional groups. The inorganic phase of the C-BG-LyPRF scaffold was composed of sodium, calcium, silicon, and phosphorus, as determined by EDX analysis. Furthermore, C-BG-LyPRF scaffold was biocompatible with MC3T3-E1 cells in both the Live/Dead and prolif-eration assays. Data demonstrate the developed C-BG-LyPRF scaffold exhibits biomimetic and biocompatibility properties, establishing it as a promising biomaterial for craniofacial regeneration. [ABSTRACT FROM AUTHOR]

The increasing demand for bone grafts due to the aging population has opened new opportunities for the manufacture of porous ceramics to assist in bone reconstruction. In our study, we investigate a new, promising method to manufacture hierarchically porous structures in a straightforward and tunable way. It consists of combining the novel technology of capillary suspensions, formed by mixing solid particles and two immiscible liquids, one less than 5 vol%, with freeze casting. We have successfully achieved alumina and beta‐tricalcium phosphate (β‐TCP) materials with both <2 µm and 20–50 µm as the smallest and largest pore sizes, respectively. The microstructure exhibits fully open pores and high levels of porosity (>60%). The capillary suspensions’ rheological behavior indicates that silica nano‐suspensions as a secondary fluid creates a stronger internal particle network than sucrose for the alumina system. Conversely, the opposite was observed with the β‐TCP system. These differences were attributed to the change in affinity between the secondary fluids and the solid loading. In our study, both systems have served to deepen the knowledge about the new area of capillary suspensions and proved their use in hierarchical porous scaffolds for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Robocasting is a highly effective method to fabricate 3D bone scaffolds for bone tissue regeneration as it offers precise material deposition and great control over pore size and interconnectivity at low cost. In this study, bentonite (BEN)–hydroxyapatite (HAP) scaffolds reinforced with graphene (G) and graphene oxide (GO) in varying concentrations separately were fabricated through robocasting. All the fabricated scaffolds were sintered at 1100 °C. However, the BEN–HAP scaffolds (BH) were sintered in normal air and a controlled Argon atmosphere was used for the GBH and GOBH scaffolds. The printed samples were subjected to physical and mechanical characterizations. The results revealed that the higher concentrations of G and GO (2GBH and 2GOBH) resulted in decreased density and modified water absorption patterns. The compression test among the scaffold groups shows higher strength in graphene reinforced scaffolds than graphene oxide, making them appropriate for load-bearing bone tissue engineering applications. FTIR and XRD data revealed the chemical and structural changes in the scaffolds. The rough surface morphology of the printed scaffolds was analysed via FESEM. The EDAX data confirmed the presence of calcium, iron, alumina, magnesium, silica, phosphate, and sodium ions in both the GBH and GOBH scaffolds. The assessment of biological characterization through MTT and live–dead assays shows no cytotoxic effect among the scaffolds. However, the higher concentrations of graphene oxide were shown to reduce the cell viability. The findings of this study emphasize the interplay between scaffold composition, structural properties, and biological outcomes. [ABSTRACT FROM AUTHOR]

Background: Shoulder pain and disability from rotator cuff tears remain challenging clinical problem despite advancements in surgical techniques and materials. To advance our understanding of injury progression and develop effective therapeutics using tissue engineering and regenerative medicine approaches, it is crucial to develop and utilize animal models that closely resemble the anatomy and display the pathophysiology of the human rotator cuff. Among various animal models, the rabbit shoulder defect model is particularly favored due to its similarity to human rotator cuff pathology. However, a standardized protocol for creating a massive rotator cuff defect in the rabbits is not well defined. Therefore, the objective of our study was to establish a robust and reproducible model of a rotator cuff defect to evaluate the regenerative efficacy of scaffolds. Results: In our study, we successfully developed a rabbit model with a massive supraspinatus tendon defect that closely resembles the common rotator cuff injuries observed in humans. This defect involved a complete transection of the tendon, spanning 10 mm in length and encompassing its full thickness and width. To ensure stable scaffolding, we employed an innovative bridging suture technique that utilized a modified Mason-Allen suture as a structural support. Moreover, to assess the therapeutic effectiveness of the model, we utilized different scaffolds, including a bovine tendon extracellular matrix (ECM) scaffold and a commercial acellular dermal matrix (ADM) scaffold. Throughout the observation period, no scaffold damage was observed. Notably, comprehensive histological analysis demonstrated that the regenerative tissue in the tendon ECM scaffold group exhibited an organized and aligned fiber structure, indicating tendon-like tissue regeneration while the tissue in the ADM group showed comparatively less organization. Conclusions: This study presents a comprehensive description of the implemented procedures for the development of a highly reproducible animal model that induces massive segmental defects in rotator cuff tendons. This protocol can be universally implemented with alternative scaffolds to investigate extensive tendon defects and evaluate the efficacy of regenerative treatments. The application of our animal model offers a standardized and reproducible platform, enabling researchers to systematically evaluate, compare, and optimize scaffold designs. This approach holds significant importance in advancing the development of tissue engineering strategies for effectively repairing extensive tendon defects. [ABSTRACT FROM AUTHOR]

Background: Craniofacial bone regeneration represents a dynamic area within tissue engineering and regenerative medicine. Central to this field, is the continual exploration of new methodologies for template fabrication, leveraging established bio ceramic materials, with the objective of restoring bone integrity and facilitating successful implant placements. Methods: Photopolymerized templates were prepared using three distinct bio ceramic materials, specifically a wet chemically synthesized bioactive glass and two commercially sourced hydroxyapatite variants. These templates underwent comprehensive characterization to assess their physicochemical and mechanical attributes, employing techniques including Fourier transform infrared spectroscopy, scanning electron microscopy, and nano-computed tomography. Evaluation of their biocompatibility was conducted through interaction with primary human osteoblasts (hOB) and subsequent examination using scanning electron microscopy. Results: The results demonstrated that composite showed intramolecular hydrogen bonding interactions with the photopolymer, while computerized tomography unveiled the porous morphology and distribution within the templates. A relatively higher porosity percentage (31.55 ± 8.70%) and compressive strength (1.53 ± 0.11 MPa) was noted for bioactive glass templates. Human osteoblast cultured on bioactive glass showed higher viability compared to other specimens. Scanning micrographs of human osteoblast on templated showed cellular adhesion and the presence of filopodia and lamellipodia. Conclusion: In summary these templates have the potential to be used for alveolar bone regeneration in critical size defect. Photopolymerization of bioceramics may be an interesting technique for scaffolds fabrication for bone tissue engineering application but needs more optimization to overcome existing issues like the ideal ratio of the photopolymer to bioceramics. [ABSTRACT FROM AUTHOR]

This paper presents a novel approach to the correction of zygomatic malposition and secondary reconstruction orbital floor fractures, highlighting the use of hydrated acellular dermal matrix (ADM), specifically CGDerm One-Step, in a case where traditional solid implants failed to maintain structural integrity and volume. A 27-year-old woman with persistent facial deformities following a traumatic incident underwent a transformative procedure that utilized ADM for volume correction and structural support, addressing significant challenges such as enophthalmos and facial contour depression. This approach was necessitated by the descent of the entire orbital floor and a previously placed implant (Medpor), leading to unsatisfactory volume correction. By integrating ADM with titanium-reinforced fan plates (Synpor), the surgery successfully restored the patient's facial symmetry and addressed her functional concerns, including diplopia and limited eye movement. Postoperative evaluations demonstrated the long-term effectiveness of this method, with significant improvements in facial contour and eye symmetry. Our findings suggest that ADM, particularly in its hydrated form, offers a reliable alternative to traditional bone grafts and implants for correcting complex craniofacial deformities, providing both aesthetic and functional benefits. This case underscores the importance of adaptable, tissue-mimicking materials in facial reconstructive surgery, offering insights into their potential for broader application in post-traumatic facial corrections. [ABSTRACT FROM AUTHOR]